A Single-Blind, Randomized, Placebo-Controlled Trial of Human Fecal Microbiota Transplantation for the Therapy of Pediatric Ulcerative Colitis and Inflammatory Bowel Disease Unclassified

BACKGROUND:

Approximately 104,000 Canadians are affected by ulcerative colitis (UC), an inflammatory bowel disease characterized by immune dysregulation. Ontario, Canada has some of the highest rates of childhood-onset UC in the world and this disease can be particularly debilitating in childhood. Effects on growth and development are profound in pediatric onset disease, and existing treatments, which include long-term immunosuppression, carry short and long-term risks of infection, malignancy, and toxicity.

The intestinal bacteria has a critical role in the regulation of the immune system. Fecal microbiota transplantation (FMT), the transfer of intestinal bacteria from a healthy donor to a recipient, has been shown to treat recurrent Clostridium difficile intestinal infections. The therapeutic potential of FMT for UC has been demonstrated in a recent adult UC trial at our institution (primary investigator: Dr. Paul Moayyedi; collaborator on the PediFETCh trial). Randomized, placebo-controlled trials of FMT in pediatric inflammatory bowel disease are nonexistent. FMT may present a valuable, safer therapeutic option for pediatric UC and a randomized-controlled trial is needed.

Four small case-series have demonstrated success of FMT for pediatric inflammatory bowel disease (IBD). Protocols and response rates varied across each study, but lower gastrointestinal tract administration yielded clinical response rates in 67-100% of patients. Two single--center pediatric case reports have been recently published showing marked clinical improvement in two patients with severe colitis. A 2015 case report described an 18 -month old female presenting with an early -onset colitis with UC- like presentation. She responded after 7 serial FMT infusions with donor stool from an age-matched niece and older brother. A 2016 case report described an 11 -year old female with steroid dependent UC who responded after serial FMT infusions every 2 to 4 weeks over a 10 month period. The patient remained in clinical remission at 40 weeks post final FMT, and showed complete endoscopic healing. A further 2016 case report described a 3-year old female with acute severe UC who was refractory to aminosalicylates and all immunosuppressive drugs. She received 6 successive FMT enemas and 4 FMT via nasoduodenal tube over 10 days. While this patient ultimately required colectomy, she did not show any significant long-term side effects as a result of the trial of FMT.

Strong evidence exists in adult studies to support the use of FMT in UC treatment. Four randomized-controlled trials (RCTs), considered one of the highest qualities of clinical trial evidence, have been published to date. Slight variations in protocol existed across all four studies, but taken together, the overall clinical and endoscopic remission rates in patients who received FMT were an impressive: 42.1% and 26.4%, respectively.